Tumor lysis syndrome (TLS) is the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers.
Pathophysiology
TLS is a metabolic disturbance caused by rapid destruction of cancer cells or following the initiation of cytotoxic therapy and the release of their toxic contents into the blood stream. Cancer cells may die as part of their cell cycle even without treatment, such as in a highly proliferative cancer like leukemia, or, typically, after treatment with chemotherapeutic drugs. As the cancer cells die, they release large amounts of intracellular potassium, phosphate and purine nucleotides. In fact, dying cancer cells start releasing potassium even before they lyse. There is more potassium, phosphorus, nucleic acids, and cytokines than the body’s homeostatic mechanisms can deal with. The kidneys are primarily involved in excreting urate, xanthine (metabolic by-product of nucleic acid), and phosphate, which can precipitate and form cystals in any part of the renal system. The accumulation of toxic products and uric acid crystals, as well as other drug, physical, and physiological insults to the kidney (see figure below) can lead to acute renal failure (ARF) before the clinical signs of TLS become evident.
TLS can result in life-threatening hemodynamic and renal complications if it is not managed correctly. Despite several advances in supportive care and monitoring, TLS still poses considerable danger to many patients with cancer. Most of the severe complications of TLS can be prevented through measures, such as hydration, alkalinization, and use of the uric acid-lowering agents allopurinol and rasburicase. Nursing assessment and management is essential in preventing and treating TLS.
Characteristics that put a patient at risk for TLS are:
Tumor with a high proliferative rate (rapid division and growth); tumor with a high sensitivity to chemotherapy; and tumor of large size, i.e. “bulky disease”.
Decreased kidney function and elevated lactate dehydrogenase (LDH) at baseline also increases risk.
Most often, TLS is associated with the administration of induction chemotherapy, but it has been reported to occur with radiation therapy, corticosteroids, hormonal agents, biologics, monoclonal antibodies, intrathecal chemotherapy and chemo-embolization.
TLS may even occur spontaneously, before the initiation of therapy.
Signs & Symptoms
Signs and symptoms of TLS may be evident within a few hours after the start of chemotherapy but more often within 24 to 48 hours. The release of large amounts of potassium that the kidneys cannot completely excrete, leads to hyperkalemia, which can result in cardiac arrhythmias. Likewise, kidney dysfunction results in hyperphosphatemia, hyperuricemia, and hypocalcemia, which lead to several manifestations:
Diagnosis Criteria
A commonly accepted definition of TLS includes a laboratory component and a clinical component.
"Laboratory" TLS includes two or more of the following:
* Serum Uric acid greater than or equal to 8 mg/dl –OR- a 25% increase from baseline
Serum Potassium greater than or equal to 6 mEq/dl –OR- a 25% increase from baseline
Serum Phosphorous greater than or equal to 6.5 mg/dl –OR- a 25% increase from baseline
Serum Calcium less than or equal to 7 mg/dl –OR- a 25% decrease from baseline
"Clinical" TLS includes laboratory TLS plus one of the following:
Serum creatinine greater than or equal to 1.5 times the upper limit
Cardiac arrhythmias or sudden cardiac death
Seizures
Radiology
Radiologic procedures to assess TLS risk typically include a chest x-ray and renal ultrasound. Use of IV contrast material should be avoided in these procedures because of the additional stress it places on the kidneys to excrete the “heavy” contrast substance. Chest and abdominal computed tomography (CT) scans are also frequently used to assess tumor size and location, in addition to assessing risk for TLS. Pay special attention to the abdomen in radiologic scans because renal dysfunction may be caused by the lymphoma pressing on the renal artery limiting blood flow to the kidneys or the kidney itself. In this case, the patient would need intervention to correct these prior to the start of therapy. (Secola, 2006)
Prophylactic prevention & management of TLS
Start central venous access and place on an oncology or intensive care unit
Obtain baseline electrocardiogram
Ensure rigorous hydration - approximately 3 L/m2/day to maintain urine output of at least 100 mL/m2/day. If necessary, diuretics such as furosemide and/or mannitol may be used to maintain urine output.
Obtain baseline lab values including: LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium. Check these values q6-8 hr for the first 48 to 72 hr after therapy, and then tapered according to risk.
Administer allopurinol 200 - 300 mg/m2/day or rasburicase 0.20 mg/kg/day, IV over 30 min for 3 to 7 days.
(Optional) Alkalinization of urine with sodium bicarbonate in IV fluids.
Medications
Allopurinol Allopurinol has been used for some time now to help prevent TLS. It blocks uric acid production by inhibiting xanthine oxidase, and it is effective in preventing further development or buildup of uric acid. Allopurinol is predominantly administered orally. It is also available in an IV formulation. For young children, the tablets must be crushed up and administered 3 times a day, but it is easily given. Because allopurinol does not typically produce an immediate response, it may not provide enough renal protection for high-risk patients. It also does not affect the uric acid that has already formed, which is a concern in patients with an elevated level of uric acid. Allopurinol administration can also result in hypoxanthine and xanthine accumulation.
Rasburicase Rasburicase is a newer uric acid-lowering agent, and it is currently the only pharmacologic alternative to allopurinol. It is a recombinant urate-oxidase enzyme derived from the Aspergillus flavus gene, and it works by oxidizing uric acid into the water-soluble substance allantoin, which the kidney excretes easily. Nurses administering rasburicase should be aware that its rapid action can degrade uric acid in blood samples at room temperature, resulting in an artificially low level of uric acid. Therefore, when obtaining tumor lysis laboratory values, blood samples should be collected in prechilled heparin tubes, immediately placed in ice, and should be analyzed within 4 hours of collection.
Nursing Interventions
Nursing interventions should include monitoring of urine output and alkalinization, when sodium bicarbonate is used. Any decrease in output should be reported; diuretics should be given and/or IV fluids should be adjusted accordingly.
1. Observe for fluid overload - Monitor weight, output, vital signs and respiratory status. Hydration is the first and most important line of prevention. IV fluid should be 3000 mL/m2/24 hours or more (amount may vary depending on age and comorbidities) and continued for several days to maintain a urine output of more than 100 cc/m2/hour and a urine specific gravity of less than 1.010. It is especially important to work with physicians and residents to ensure that the patient receives no additional potassium during hydration, even if the patient’s potassium level is normal because the patient will be exposed to an elevated level of potassium when lysis begins.
2. Monitor laboratory values and avoid using nephrotoxic medications (aminoglycoside antibiotics, NSAIDs). Tumor lysis laboratory values should be obtained every 6 to 12 hours minimum, especially during the first few days of treatment. The nurse also should continuously monitor cardiac, respiratory, neuromuscular, and gastrointestinal function, in addition to checking for edema and weight changes.
3. It may be necessary to institute a RENAL DIET, which is low in potassium and phosphorus. (Contact Dietitian)
Limiting fluids
Eating a low-protein diet (this may be recommended)
Restricting salt, potassium, phosphorous, and other electrolytes
Getting enough calories if weight loss is present.
The Renal Diet
The following information was obtained from DaVita
Patients sometimes have problems remembering which foods contain potassium and which ones have phosphorus, partly because some foods are high in both potassium and phosphorus. These are the "double jeopardy" foods that are best to avoid or use in very small amounts.
Most high potassium foods come from plants. Fruits and vegetables tend to be the high potassium sources.
High phosphorus foods are mainly from animals. High-protein foods, such as meats, along with dried beans and peas tend to be high in phosphorus.
Double jeopardy foods that are high in both potassium and phosphorus include dairy foods, nuts, seeds, chocolate and whole grain foods.
High potassium
High phosphorus
Double jeopardy —High in potassium & phosphorus
Fruits
Vegetables
Meat
Poultry
Fish and seafood
Wild game
Eggs
Dried beans and peas
Milk
Dairy products
Nuts and seeds
Chocolate
Whole grain products
For some of the double jeopardy foods (on the left), there are alternatives (on the right) that will help keep potassium and phosphorus under control.
Low-salt snack foods including pretzels,tortilla chips, popcorn, crackers, Sun Chips®
Peanut butter
Low-fat cream cheese, jam or fruit spread
An extra caution about phosphorus Foods, such as deli meats and colas, which have phosphates added in processing, are especially high in phosphorus. Phosphates are often used as a preservative or as an ingredient in processed foods. For that reason, encourage patients to read food labels carefully and look for words that mean phosphorus in the ingredient section such as the ones below:
Phosphoric acid
Dicalcium phosphate
Monocalcium phosphate
Pyrophosphates
Hexametaphosphate
Polyphosphates
Sodium phosphate
These ingredients used as preservatives may be more easily absorbed than phosphorus from natural food sources. That is why it’s important to avoid foods with these ingredients.
Other foods the patient may be instructed to limit or avoid are sweets and salty foods such as the following:
Candy (candy bars, hard candy, chocolate, jelly beans, gum drops)
Regular sugar
Syrup (maple, chocolate)
Honey
Molasses
Pies, cakes, cookies, donuts
Ice cream
Canned foods
BBQ sauce, ketchup
Onion, garlic or table salt
TV dinners
Meat tenderizer
Marinades
Nuts
Pizza
Salted chips and snacks
Soy Sauce
Worcestershire sauce
The following can be consumed by someone on a renal diet:
Carbohydrate foods
Milk and nondairy
skim or fat-free milk, non-dairy creamer, plain yogurt, sugar-free yogurt, sugar-free pudding, sugar-free ice cream, sugar-free nondairy frozen desserts* *Portions of dairy products are often limited to 4 ounces due to high protein, potassium or phosphorus content
Breads and starches
white bread, unsweetened, refined dry cereals, cream of wheat, grits, malt-o-meal, noodles, pasta, rice, bagel (small), hamburger bun, unsalted crackers, cornbread (made from scratch), flour tortilla
Fruits and juices
apples, apple juice, applesauce, apricot halves, berries including: strawberries, raspberries, cranberries, blackberries and blueberries, low sugar cranberry juice, cherries, fruit cocktail, grapefruit, grapes, grape juice, kumquats, mandarin oranges, pears, pineapple, plums, tangerine, watermelon Note: Fruit canned in unsweetened juice is usually recommended.
Starchy vegetables
corn, peas, mixed vegetables with corn and peas (eat these less often because they are high in phosphorus), potatoes (soaked to reduce potassium, if needed)
Nonstarchy vegetables
asparagus, beets, broccoli, Brussel sprouts, carrots, cabbage, cauliflower, celery, cucumber, eggplant, frozen broccoli cuts, green beans, iceberg lettuce, kale, leeks, mustard greens, okra, onions, red and green peppers, radishes, raw spinach (1/2 cup), snow peas, summer squash, turnips
Higher protein foods
Meats, cheeses and eggs
lean cuts of meat, poultry, fish and seafood; eggs, low cholesterol egg substitute; cottage cheese (limited due to high sodium content)
Higher fat foods
Seasoning and calories
soft or tub margarine low in trans fats, mayonnaise, sour cream, cream cheese, low fat mayonnaise, low fat sour cream, low fat cream cheese
Beverages
Beverages
water, Crystal Light®, diet clear sodas (Diet Sprite®, diet gingerale), homemade tea or lemonade sweetened with an artificial sweetener
For Renal friendly recipes please visit:
Teaching for Patients and Family Members
Education for the patient and family should include symptoms to be reported, a discussion of the patient's typical diet, and what foods should be avoided (those high in potassium & phosphorus; bananas, oranges, tomatoes, milk products, prepared/processed foods, sodas, chocolate and nuts). The patient should be encouraged to maintain adequate fluid intake and be aware of the need for accurate input and output monitoring. This can be a very scary time for patients, and thus the support of a knowledgeable nurse can make all the difference.
The materials presented above were obtained from the following literature:
Journal articles
Howard, S.C., Jones, D.P., and Pui, C. The Tumor Lysis Syndrome, 2011, The New England Journal of Medicine, 364(19), 1844-1854
Secola, R., Tumor Lysis Syndrome: Nursing Management and New Therapeutic Options, 2006, Proceedings of the Johns Hopkins Advanced Studies in Nursing, 4(3), 41-48
Tumor Lysis Syndrome (TLS)
Tumor lysis syndrome (TLS) is the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers.
Pathophysiology
TLS is a metabolic disturbance caused by rapid destruction of cancer cells or following the initiation of cytotoxic therapy and the release of their toxic contents into the blood stream. Cancer cells may die as part of their cell cycle even without treatment, such as in a highly proliferative cancer like leukemia, or, typically, after treatment with chemotherapeutic drugs. As the cancer cells die, they release large amounts of intracellular potassium, phosphate and purine nucleotides. In fact, dying cancer cells start releasing potassium even before they lyse. There is more potassium, phosphorus, nucleic acids, and cytokines than the body’s homeostatic mechanisms can deal with. The kidneys are primarily involved in excreting urate, xanthine (metabolic by-product of nucleic acid), and phosphate, which can precipitate and form cystals in any part of the renal system. The accumulation of toxic products and uric acid crystals, as well as other drug, physical, and physiological insults to the kidney (see figure below) can lead to acute renal failure (ARF) before the clinical signs of TLS become evident.
TLS can result in life-threatening hemodynamic and renal complications if it is not managed correctly. Despite several advances in supportive care and monitoring, TLS still poses considerable danger to many patients with cancer. Most of the severe complications of TLS can be prevented through measures, such as hydration, alkalinization, and use of the uric acid-lowering agents allopurinol and rasburicase.
Nursing assessment and management is essential in preventing and treating TLS.
Characteristics that put a patient at risk for TLS are:
Signs & Symptoms
Signs and symptoms of TLS may be evident within a few hours after the start of chemotherapy but more often within 24 to 48 hours. The release of large amounts of potassium that the kidneys cannot completely excrete, leads to hyperkalemia, which can result in cardiac arrhythmias. Likewise, kidney dysfunction results in hyperphosphatemia, hyperuricemia, and hypocalcemia, which lead to several manifestations:
Diagnosis Criteria
A commonly accepted definition of TLS includes a laboratory component and a clinical component."Laboratory" TLS includes two or more of the following:
* Serum Uric acid greater than or equal to 8 mg/dl –OR- a 25% increase from baseline"Clinical" TLS includes laboratory TLS plus one of the following:
Radiology
Radiologic procedures to assess TLS risk typically include a chest x-ray and renal ultrasound. Use of IV contrast material should be avoided in these procedures because of the additional stress it places on the kidneys to excrete the “heavy” contrast substance. Chest and abdominal computed tomography (CT) scans are also frequently used to assess tumor size and location, in addition to assessing risk for TLS. Pay special attention to the abdomen in radiologic scans because renal dysfunction may be caused by the lymphoma pressing on the renal artery limiting blood flow to the kidneys or the kidney itself. In this case, the patient would need intervention to correct these prior to the start of therapy.(Secola, 2006)
Prophylactic prevention & management of TLS
Medications
Allopurinol
Allopurinol has been used for some time now to help prevent TLS. It blocks uric acid production by inhibiting xanthine oxidase, and it is effective in preventing further development or buildup of uric acid. Allopurinol is predominantly administered orally. It is also available in an IV formulation. For young children, the tablets must be crushed up and administered 3 times a day, but it is easily given. Because allopurinol does not typically produce an immediate response, it may not provide enough renal protection for high-risk patients. It also does not affect the uric acid that has already formed, which is a concern in patients with an elevated level of uric acid. Allopurinol administration can also result in hypoxanthine and xanthine accumulation.
Rasburicase
Rasburicase is a newer uric acid-lowering agent, and it is currently the only pharmacologic alternative to allopurinol. It is a recombinant urate-oxidase enzyme derived from the Aspergillus flavus gene, and it works by oxidizing uric acid into the water-soluble substance allantoin, which the kidney excretes easily.
Nurses administering rasburicase should be aware that its rapid action can degrade uric acid in blood samples at room temperature, resulting in an artificially low level of uric acid. Therefore, when obtaining tumor lysis laboratory values, blood samples should be collected in prechilled heparin tubes, immediately placed in ice, and should be analyzed within 4 hours of collection.
Nursing Interventions
Nursing interventions should include monitoring of urine output and alkalinization, when sodium bicarbonate is used. Any decrease in output should be reported; diuretics should be given and/or IV fluids should be adjusted accordingly.1. Observe for fluid overload - Monitor weight, output, vital signs and respiratory status.
Hydration is the first and most important line of prevention. IV fluid should be 3000 mL/m2/24 hours or more (amount may vary depending on age and comorbidities) and
continued for several days to maintain a urine output of more than 100 cc/m2/hour and a urine specific gravity of less than 1.010. It is especially important to work with
physicians and residents to ensure that the patient receives no additional potassium during hydration, even if the patient’s potassium level is normal because the patient will
be exposed to an elevated level of potassium when lysis begins.
2. Monitor laboratory values and avoid using nephrotoxic medications (aminoglycoside antibiotics, NSAIDs).
Tumor lysis laboratory values should be obtained every 6 to 12 hours minimum, especially during the first few days of treatment. The nurse also should continuously monitor
cardiac, respiratory, neuromuscular, and gastrointestinal function, in addition to checking for edema and weight changes.
3. It may be necessary to institute a RENAL DIET, which is low in potassium and phosphorus. (Contact Dietitian)
The Renal Diet
The following information was obtained from DaVitaPatients sometimes have problems remembering which foods contain potassium and which ones have phosphorus, partly because some foods are high in both potassium and phosphorus. These are the "double jeopardy" foods that are best to avoid or use in very small amounts.
Double Jeopardy Foods (High Potassium &
Alternatives
Foods, such as deli meats and colas, which have phosphates added in processing, are especially high in phosphorus. Phosphates are often used as a preservative or as an ingredient in processed foods. For that reason, encourage patients to read food labels carefully and look for words that mean phosphorus in the ingredient section such as the ones below:
- Phosphoric acid
- Dicalcium phosphate
- Monocalcium phosphate
- Pyrophosphates
- Hexametaphosphate
- Polyphosphates
- Sodium phosphate
These ingredients used as preservatives may be more easily absorbed than phosphorus from natural food sources. That is why it’s important to avoid foods with these ingredients.Other foods the patient may be instructed to limit or avoid are sweets and salty foods such as the following:
The following can be consumed by someone on a renal diet:
Carbohydrate foods*Portions of dairy products are often limited to 4 ounces due to high protein, potassium or phosphorus content
Note: Fruit canned in unsweetened juice is usually recommended.
For Renal friendly recipes please visit:
Teaching for Patients and Family Members
Education for the patient and family should include symptoms to be reported, a discussion of the patient's typical diet, and what foods should be avoided (those high in potassium & phosphorus; bananas, oranges, tomatoes, milk products, prepared/processed foods, sodas, chocolate and nuts). The patient should be encouraged to maintain adequate fluid intake and be aware of the need for accurate input and output monitoring. This can be a very scary time for patients, and thus the support of a knowledgeable nurse can make all the difference.The materials presented above were obtained from the following literature:
Journal articles
Howard, S.C., Jones, D.P., and Pui, C. The Tumor Lysis Syndrome, 2011, The New England Journal of Medicine, 364(19), 1844-1854Held-Warmkessel, J. How to Prevent and Manage Tumor Lysis Syndrome, 2010, Nursing2010, 26-31
Secola, R., Tumor Lysis Syndrome: Nursing Management and New Therapeutic Options, 2006, Proceedings of the Johns Hopkins Advanced Studies in Nursing, 4(3), 41-48
Arrambide, K, and Toto, R.D., Tumor Lysis Syndrome, 1993, Seminars in Nephrology, 13(3), 273-280
Website references & resources
OncoLink - Abramson Cancer Center of the University of Pennsylvania
Allopurinol info: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000746/
Rasburicase info: http://www.elitekinfo.com/